Fast Optical Imaging of Human Brain Function

Great advancements in brain imaging during the last few decades have opened a large number of new possibilities for neuroscientists. The most dominant methodologies (electrophysiological and magnetic resonance-based methods) emphasize temporal and spatial information, respectively. However, theorizing about brain function has recently emphasized the importance of rapid (within 100 ms or so) interactions between different elements of complex neuronal networks. Fast optical imaging, and in particular the event-related optical signal (EROS, a technology that has emerged over the last 15 years) may provide descriptions of localized (to sub-cm level) brain activity with a temporal resolution of less than 100 ms. The main limitations of EROS are its limited penetration, which allows us to image cortical structures not deeper than 3 cm from the surface of the head, and its low signal-to-noise ratio. Advantages include the fact that EROS is compatible with most other imaging methods, including electrophysiological, magnetic resonance, and trans-cranial magnetic stimulation techniques, with which can be recorded concurrently. In this paper we present a summary of the research that has been conducted so far on fast optical imaging, including evidence for the possibility of recording neuronal signals with this method, the properties of the signals, and various examples of applications to the study of human cognitive neuroscience. Extant issues, controversies, and possible future developments are also discussed

Spread of activation and deactivation in the brain: Does age matter?

Cross-sectional aging fMRI results are sometimes difficult to interpret, as standard measures of activation and deactivation may confound variations in signal amplitude and spread, which however may be differentially affected by age-related changes in various anatomical and physiological factors. To disentangle these two types of measures, here we propose a novel method to obtain independent estimates of the peak amplitude and spread of the BOLD signal in areas activated (task-positive) and deactivated (task-negative) by a Sternberg task, in 14 younger and 28 older adults. The peak measures indicated that, compared to younger adults, older adults had increased activation of the task-positive network, but similar levels of deactivation in the task-negative network. Measures of signal spread revealed that older adults had an increased spread of activation in task-positive areas, but a starkly reduced spread of deactivation in task-negative areas. These effects were consistent across regions within each network. Further, there was greater variability in the anatomical localization of peak points in older adults, leading to reduced cross-subject overlap. These results reveal factors that may confound the interpretation of studies of aging. Additionally, spread measures may be linked to local connectivity phenomena and could be particularly useful to analyze age-related deactivation patterns, complementing the results obtained with standard peak and ROI analyses

The influence of posterior parietal cortex on extrastriate visual activity: A concurrent TMS and fast optical imaging study

The posterior parietal cortex (PPC) is a critical node in attentional and saccadic eye movement networks of the cerebral cortex, exerting top-down control over activity in visual cortex. Here, we sought to further elucidate the properties of PPC feedback by providing a time-resolved map of functional connectivity between parietal and occipital cortex using single-pulse TMS to stimulate the left PPC while concurrently recording fast optical imaging data from bilateral occipital cortex. Magnetic stimulation of the PPC induced transient ipsilateral occipital activations (BA 18) 24 to 48ms post-TMS. Concurrent TMS and fast optical imaging results demonstrate a clear influence of PPC stimulation on activity within human extrastriate visual cortex and further extend this time- and space-resolved method for examining functional connectivity

To See or Not to See: Prestimulus α Phase Predicts Visual Awareness

We often fail to see something that at other times is readily detectable. Because the visual stimulus itself is unchanged, this variability in conscious awareness is likely related to changes in the brain. Here we show that the phase of EEG α rhythm measured over posterior brain regions can reliably predict both subsequent visual detection and stimulus-elicited cortical activation levels in a metacontrast masking paradigm. When a visual target presentation coincides with the trough of an α wave, cortical activation is suppressed as early as 100 ms after stimulus onset, and observers are less likely to detect the target. Thus, during one α cycle lasting 100 ms, the human brain goes through a rapid oscillation in excitability, which directly influences the probability that an environmental stimulus will reach conscious awareness. Moreover, ERPs to the appearance of a fixation cross before the target predict its detection, further suggesting that cortical excitability level may mediate target detection. A novel theory of cortical inhibition is proposed in which increased α power represents a “pulsed inhibition” of cortical activity that affects visual awareness

Monomer–dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies

To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer–oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein–uPAR in live cells, we analyzed the effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics and dimerization at the cell membrane. Vitronectin directs the recruitment of dimers and slows down the diffusion of the receptors at the basal membrane. The commitment to uPA–plasminogen activator inhibitor type 1–mediated endocytosis and recycling modifies uPAR diffusion and induces an exchange between uPAR monomers and dimers. This exchange is fully reversible. The data demonstrate that cell surface protein assemblies are important in regulating the dynamics and localization of uPAR at the cell membrane and the exchange of monomers and dimers. These results also provide a strong rationale for dynamic studies of GPI-anchored molecules in live cells at steady state and in the absence of cross-linker/clustering agents

Comparing aging and fitness effects on brain anatomy

Recent studies suggest that cardiorespiratory fitness (CRF) mitigates the brain’s atrophy typically associated with aging, via a variety of beneficial mechanisms. One could argue that if CRF is generally counteracting the negative effects of aging, the same regions that display the greatest age-related volumetric loss should also show the largest beneficial effects of fitness. To test this hypothesis we examined structural MRI data from 54 healthy older adults (ages 55–87), to determine the overlap, across brain regions, of the profiles of age and fitness effects. Results showed that lower fitness and older age are associated with atrophy in several brain regions, replicating past studies. However, when the profiles of age and fitness effects were compared using a number of statistical approaches, the effects were not entirely overlapping. Interestingly, some of the regions that were most influenced by age were among those not influenced by fitness. Presumably, the age-related atrophy occurring in these regions is due to factors that are more impervious to the beneficial effects of fitness. Possible mechanisms supporting regional heterogeneity may include differential involvement in motor function, the presence of adult neurogenesis, and differential sensitivity to cerebrovascular, neurotrophic and metabolic factors

Pulsed out of awareness: EEG alpha oscillations represent a pulsed-inhibition of ongoing cortical processing

Alpha oscillations are ubiquitous in the brain, but their role in cortical processing remains a matter of debate. Recently, evidence has begun to accumulate in support of a role for alpha oscillations in attention selection and control. Here we first review evidence that 8–12 Hz oscillations in the brain have a general inhibitory role in cognitive processing, with an emphasis on their role in visual processing. Then, we summarize the evidence in support of our recent proposal that alpha represents a pulsed-inhibition of ongoing neural activity. The phase of the ongoing electroencephalography can influence evoked activity and subsequent processing, and we propose that alpha exerts its inhibitory role through alternating microstates of inhibition and excitation. Finally, we discuss evidence that this pulsed-inhibition can be entrained to rhythmic stimuli in the environment, such that preferential processing occurs for stimuli at predictable moments. The entrainment of preferential phase may provide a mechanism for temporal attention in the brain. This pulsed inhibitory account of alpha has important implications for many common cognitive phenomena, such as the attentional blink, and seems to indicate that our visual experience may at least some times be coming through in waves

Examining neural correlates of skill acquisition in a complex videogame training program

Acquisition of complex skills is a universal feature of human behavior that has been conceptualized as a process that starts with intense resource dependency, requires effortful cognitive control, and ends in relative automaticity on the multi-faceted task. The present study examined the effects of different theoretically based training strategies on cortical recruitment during acquisition of complex video game skills. Seventy-five participants were recruited and assigned to one of three training groups: (1) Fixed Emphasis Training (FET), in which participants practiced the game, (2) Hybrid Variable-Priority Training (HVT), in which participants practiced using a combination of part-task training and variable priority training, or (3) a Control group that received limited game play. After 30 h of training, game data indicated a significant advantage for the two training groups relative to the control group. The HVT group demonstrated enhanced benefits of training, as indexed by an improvement in overall game score and a reduction in cortical recruitment post-training. Specifically, while both groups demonstrated a significant reduction of activation in attentional control areas, namely the right middle frontal gyrus, right superior frontal gyrus, and the ventral medial prefrontal cortex, participants in the control group continued to engage these areas post-training, suggesting a sustained reliance on attentional regions during challenging task demands. The HVT group showed a further reduction in neural resources post-training compared to the FET group in these cognitive control regions, along with reduced activation in the motor and sensory cortices and the posteromedial cortex. Findings suggest that training, specifically one that emphasizes cognitive flexibility can reduce the attentional demands of a complex cognitive task, along with reduced reliance on the motor network

Pulsed out of awareness: EEG alpha oscillations represent a pulsed-inhibition of ongoing cortical processing

Alpha oscillations are ubiquitous in the brain, but their role in cortical processing remains a matter of debate. Recently, evidence has begun to accumulate in support of a role for alpha oscillations in attention selection and control. Here we first review evidence that 8–12 Hz oscillations in the brain have a general inhibitory role in cognitive processing, with an emphasis on their role in visual processing. Then, we summarize the evidence in support of our recent proposal that alpha represents a pulsed-inhibition of ongoing neural activity. The phase of the ongoing electroencephalography can influence evoked activity and subsequent processing, and we propose that alpha exerts its inhibitory role through alternating microstates of inhibition and excitation. Finally, we discuss evidence that this pulsed-inhibition can be entrained to rhythmic stimuli in the environment, such that preferential processing occurs for stimuli at predictable moments. The entrainment of preferential phase may provide a mechanism for temporal attention in the brain. This pulsed inhibitory account of alpha has important implications for many common cognitive phenomena, such as the attentional blink, and seems to indicate that our visual experience may at least some times be coming through in waves